IL-32 Is a Host Protective Cytokine against Mycobacterium tuberculosis in Differentiated THP-1 Human Macrophages
IL-32 Is a Host Protective Cytokine against Mycobacterium tuberculosis in Differentiated THP-1 Human Macrophages
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DOI：
10.4049/jimmunol.0901913
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发表时间：
2010-04-01
影响因子：
4.4
通讯作者：
Chan, Edward D.
中科院分区：
文献类型：
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作者：
Bai, Xiyuan;Kim, Soo-Hyun;Chan, Edward D.
巨噬细胞是抵抗结核分枝杆菌的第一道防线。然而，在巨噬细胞激活杀伤不理想的情况下，结核分枝杆菌能够在细胞内存活。IL-32是最近发现的一种由结核分枝杆菌在多种细胞类型（包括人单核细胞和巨噬细胞）中诱导的细胞因子。在本研究中，我们通过稳定表达短发夹RNA （short hairpin RNA, shRNA）来沉默IL-32在分化的THP-1人巨噬细胞结核分枝杆菌感染的体外模型中的生物学意义。在表达三种不同shRNA-IL-32结构之一的THP-1细胞中抑制内源性IL-32的产生，与稳定表达混乱shRNA的THP-1细胞相比，显著降低了结核分枝杆菌对tnf - α的诱导，降低了60%，IL-10降低了30-60%，IL-8降低了40-50%，并同时增加了细胞相关结核分枝杆菌的数量。在感染结核分枝杆菌并经rIL-32刺激的THP-1细胞中，与单独感染结核分枝杆菌相比，观察到更高水平的凋亡。相反，在内源性IL-32缺失的细胞中，结核分枝杆菌诱导的细胞凋亡明显减少，caspase-3的激活也随之降低。rIL-32 γ显著降低了胞内结核分枝杆菌的活菌数量，caspase-3抑制剂可以适度但显著地消除这种作用。我们得出结论，IL-32在分化的THP-1人巨噬细胞中发挥宿主防御结核分枝杆菌的作用。中华免疫学杂志，2010,18(4):393 - 394。
Macrophages provide a first line of defense against Mycobacterium tuberculosis. However, in instances where macrophage activation for killing is suboptimal, M. tuberculosis is capable of surviving intracellularly. IL-32 is a recently described cytokine induced by M. tuberculosis in a variety of cell types including human monocytes and macrophages. In this study, we investigated the biological significance of IL-32 in an in vitro model of M. tuberculosis infection in differentiated THP-1 human macrophages in which IL-32 expression was silenced using stable expression of short hairpin RNA (shRNA). Inhibition of endogenous IL-32 production in THP-1 cells that express one of three distinct shRNA-IL-32 constructs significantly decreased M. tuberculosis induction of TNF-alpha by similar to 60%, IL-10 by 30-60%, and IL-8 by 40-50% and concomitantly increased the number of cell-associated M. tuberculosis bacteria compared with THP-1 cells stably expressing a scrambled shRNA. In THP-1 cells infected with M. tuberculosis and stimulated with rIL-32, a greater level of apoptosis was observed compared with that with M. tuberculosis infection alone. Obversely, there was significant abrogation of apoptosis induced by M. tuberculosis and a concomitant decrease in caspase-3 activation in cells depleted of endogenous IL-32. rIL-32 gamma significantly reduced the number of viable intracellular M. tuberculosis bacteria, which was modestly but significantly abrogated with a caspase-3 inhibitor. We conclude that IL-32 plays a host defense role against M. tuberculosis in differentiated THP-1 human macrophages. The Journal of Immunology, 2010,184: 3830-3840.